Trial Title:
A Study of Gilteritinib, Venetoclax and Azacitidine as a Combined Treatment for People Newly Diagnosed With Acute Myeloid Leukemia
NCT ID:
NCT05520567
Condition:
Acute Myeloid Leukemia (AML)
FLT3-mutated Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Azacitidine
Venetoclax
Gilteritinib
Conditions: Keywords:
Cancer
Acute Myeloid Leukemia
AML
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Gilteritinib
Description:
Oral
Arm group label:
Dose Expansion Cohort (Phase 2)
Arm group label:
Dose Ranging Cohort (Phase 1)
Other name:
ASP2215
Other name:
XOSPATA®
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Oral
Arm group label:
Dose Expansion Cohort (Phase 2)
Arm group label:
Dose Ranging Cohort (Phase 1)
Other name:
ABT199
Other name:
Venclexta
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
Subcutaneous injection or intravenous infusion
Arm group label:
Dose Expansion Cohort (Phase 2)
Arm group label:
Dose Ranging Cohort (Phase 1)
Summary:
People with acute myeloid leukemia (AML) are usually treated with chemotherapy. Some
people with AML have a changed FLT3 gene which causes leukemia cells to grow faster.
Therefore, chemotherapy is less suitable to treat AML in people with the changed FLT3
gene.
Gilteritinib, given with venetoclax and azacitidine, is a potential new treatment for
people with AML with the changed FLT3 gene. They cannot have chemotherapy due to old age
or other conditions. Before these combined 3 medicines are available as a treatment, the
researchers need to understand how they are processed by and act upon the body when given
together. In this study, they do this to find a suitable dose for venetoclax and to check
for potential medical problems from the treatment.
In this study, people newly diagnosed with AML who have the changed FLT3 gene and cannot
have chemotherapy can take part.
The main aims of this study are: to find suitable doses of gilteritinib, venetoclax and
azacitidine as a combined treatment; to learn how they are processed by and act upon the
body; to learn the remission rate; to check for medical problems during this treatment.
In the study, people will visit the study clinic many times. The first visit is to check
if they can take part. People will be asked about their medical history, have a medical
examination, and have their vital signs checked. Also, they will have an ECG to check
their heart rhythm and have some blood and urine samples taken for laboratory tests. They
will have a chest X-ray and a bone marrow sample will be taken. The changed FLT3 gene
will be confirmed, either by the bone marrow or a blood sample.
This study will be in 2 phases.
In Phase 1, different small groups of people will take venetoclax tablets containing
lower to higher doses in the combined treatment. The doses of gilteritinib and
azacytidine will be unchanged. This is done to find a suitable dose of venetoclax to use
in phase 2 of the study. People will take tablets of gilteritinib and venetoclax once a
day on a 28-day cycle. They will be given azacytidine as an infusion or an injection just
under the skin. This will be for 7 days at the beginning of each 28-day cycle. They will
continue cycles of treatment throughout this phase of the study.
In Phase 2, more people newly diagnosed with AML with the changed FLT3 gene will take
part. They will be treated with the suitable doses of the combined treatment worked out
from Phase 1. Treatment will be on a 28-day cycle. People will continue on cycles of
treatment throughout this phase of the study.
Researchers will work out the remission rate from this phase of the study. In each phase
of the study, people can continue with up to 12 cycles of treatment if they can manage
any medical problems. People will visit the study clinic many times during their first
treatment cycle, and less often during the next cycles. During these visits, medical
problems will be recorded and some blood samples will be taken for laboratory tests. On
some visits, people will also have their vital signs checked. Bone marrow samples will be
taken during cycle 1, and at the beginning of cycle 3. More samples will be taken during
the study from people who are not in remission.
When people have finished treatment, those who have responded well to treatment and are
in remission will be invited to continue with up to 24 more cycles of gilteritinib plus
azacitidine.
All people taking part in the study will visit the study clinic for an end-of-treatment
visit. During this visit, medical problems will be recorded and some blood samples will
be taken for laboratory tests. People will have a medical examination, an ECG, and will
have their vital signs checked. Also, a bone marrow sample will be taken. There will be a
follow-up visit 30 days later to check for medical problems. Then people will visit the
clinic or get a phone call every 3 months for up to 3 years. This is to give an update on
their current treatment for AML.
Some people can have a stem cell transplant during the study if they meet certain study
rules. They will pause their study treatment during the stem cell transplant process and
continue study treatment afterwards.
Criteria for eligibility:
Criteria:
Inclusion Criteria
- Participant has a diagnosis of previously untreated Acute Myeloid Leukemia (AML)
according to World Health Organization classification as determined by pathology
review at the treating institution.
- Participant is positive for FMS-like tyrosine kinase 3 (FLT3) mutation (internal
tandem duplication [ITD] and/or tyrosine kinase domain [TKD] [D835/I836] mutation)
in bone marrow or whole blood as determined by the central laboratory. A participant
with rapidly proliferative disease and unable to wait for the central laboratory
results can be enrolled from a local test result.
- Participant is ineligible for intensive induction chemotherapy by meeting at least 1
of the following criteria:
- Participant is >= 75 years of age with Eastern Cooperative Oncology Group
(ECOG) performance status 0, 1, or 2.
- Participant is >= 18 to 75 years of age and has any of the following
comorbidities: ECOG performance status 2 or 3, cardiac history of congestive
heart failure requiring treatment or ejection fraction <= 50% or chronic stable
angina, known history of diffusion capacity of lung for carbon monoxide (DLCO)
<= 65% or forced expiratory volume in the first second (FEVI) <= 65%,
creatinine clearance > 30 mL/min to 45 mL/min, calculated by the Cockcroft
Gault formula, moderate hepatic impairment with total bilirubin > 1.5 to < 3.0
x upper limit of normal (ULN), any other comorbidity incompatible with
intensive chemotherapy during screening and before enrollment.
- Participant must have a projected life expectancy of at least 12 weeks.
- Participant must have adequate organ and bone marrow function prior to enrollment,
as specified per protocol's laboratory parameters.
- Participant is suitable for oral administration of study drug (gilteritinib and
venetoclax) and is willing/able to swallow oral tablets/capsules.
- Participant with a known history of human immunodeficiency virus (HIV) on effective
antiretroviral therapy must have a viral load undetectable for 6 months prior to
Cycle 1 Day 1 (C1D1).
- Female participant is eligible to participate if she is not pregnant and at least
one of the following conditions apply:
- Not a woman of childbearing potential (WOCBP) OR
- WOCBP agrees to follow the contraceptive guidance starting at screening and
continue through the study treatment period, and for at least 180 days after
the final study regimen administration.
WOCBP must have a negative pregnancy test during screening.
- Female participant must agree not to breastfeed starting at screening, throughout
the study treatment period and for 60 days after the last dose of the study
treatment regimen.
- Female participant must not donate ova starting at screening, throughout the study
treatment and for 180 days after the last dose of the study treatment regimen.
- Male participant with female partner(s) of childbearing potential must agree to use
contraception starting at screening and continue through the study treatment, and
for at least 120 days after the last dose of the study treatment regimen.
- Male participant must not donate sperm starting at screening, throughout the study
treatment and for 120 days after the last dose of the study treatment regimen.
(Venetoclax may cause a decrease in spermatogenesis. Male participant considering
preservation of fertility should bank sperm before initiating treatment with
venetoclax.)
- Male participant with a pregnant or breastfeeding partner(s) must agree to remain
abstinent or use a condom for the duration of the pregnancy or time partner is
breastfeeding throughout the treatment period, and for 120 days after the final
study drug administration.
- Participant agrees not to participate in another interventional study while on
treatment in this study.
Exclusion Criteria:
- Participant with the following conditions:
- Acute promyelocytic leukemia (APL)
- Active, symptomatic central nervous system (CNS) involvement with AML
- History of myeloproliferative neoplasm (MPN), including myelofibrosis,
essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML)
with or without BCR-ABL1 translocation or AML with BCR-ABL1 translocation
- Participant previously treated with CAR-T cell therapy for AML or MDS. Exceptions
for prior treatment of AML are (i.e., the following treatments are allowed):
- Hydroxyurea for increased blast count (No washout period required. It can be
continued throughout the first cycle of therapy).
- Leukapheresis for leukocytosis (No washout period required. It can be continued
during the study).
- Preemptive treatment with retinoic acid prior to exclusion of APL < 7 days.
- Participant who is receiving treatment with any other investigational agents.
- Participant requires treatment with concomitant drugs that are strong or moderate
inducers of cytochrome P450 (CYP)3A or P glycoprotein (P-gp) during study treatment.
- Participant who has consumed grapefruit, grapefruit products, Seville oranges
(including marmalade containing Seville oranges) or starfruit <= 3 days prior to
C1D1.
- Participant with a cardiovascular disability status of New York Heart Association
(NYHA) Class >= 3.
- Participant with mean QTcF > 450 msec at screening based on local reading performed
in triplicate.
- Participant with a history of Long QT Syndrome at screening.
- Participant has been diagnosed with another malignancy within 2 years prior to
screening for the study, with the following exceptions:
- Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ
of breast;
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the
skin;
- Previous malignancy confined and surgically resected (or treated with other
modalities) with curative intent
- Participants who are on maintenance therapy for malignancies with no evidence
of active malignancy for >= 2 years and the maintenance therapy can be
discontinued.
- Participant who has an uncontrolled intercurrent illness including, but not limited
to any of the following conditions:
- Uncontrolled hypertension
- Active, uncontrolled infection (viral, bacterial or fungal): An infection
controlled with an approved or closely monitored antibiotic/antifungal
treatment is allowed.
- Symptomatic, congestive heart failure
- Unstable angina pectoris
- Chronic respiratory disease that requires continuous oxygen
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Any other illness or condition that would interfere with study compliance or
would compromise the participant's safety or study endpoints, including any
contraindications to gilteritinib, azacitidine or venetoclax listed in the
country package insert.
- Participant who has gastrointestinal disorders, malabsorption or other abnormalities
that would interfere with absorption of the oral study drug.
- Participant has active hepatitis B or C or other active hepatic disorder.
- Participant with positive hepatitis B surface antigen (HBsAg) or detectable
hepatitis B virus (HBV) deoxyribonucleic acid (DNA) are not eligible.
- Participant with negative HBsAg, positive hepatitis B core antibody and
negative hepatitis B surface antibody will be eligible if HBV DNA is
undetectable.
- For participant with a known history of chronic HBV infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated, to be eligible
for this study.
- Participant with antibodies to hepatitis C virus (HCV) will be eligible if
hepatitis C ribonucleic acid (RNA) viral load is undetectable.
- Participant with a known history of HCV infection must have been treated and
cured to be eligible for this study. Participants with HCV infection who are
currently on treatment are eligible if they have an undetectable HCV viral
load.
- Participant has had major surgery within 4 weeks prior to the first study dose.
- Participant has a known or suspected hypersensitivity to gilteritinib, azacitidine
or venetoclax or any components of the formulations used.
- Participant with recent positive test for SARS-CoV-2 ( or diagnosed with COVID-19)
and no follow up test with negative result cannot be enrolled. Participant with
contact to persons with COVID-19 and participants with signs and symptoms for
COVID-19 infection must be tested before enrolling.
- Participant who requires concomitant treatment with a strong or moderate P-gp or
CYP3A iinhibitor, with the exception of posaconazole, for antifungal prophylaxis
during cycle 1 of the Dose Ranging Phase (phase 1). Note: Posaconazole is the only
strong CYP3A inhibitor antifungal allowed during the cycle 1 DLT evaluation period.
Post-DLT evaluation period, other antifungals including strong or moderate CYP3A
inhibitors are allowed throughout the study.
- Participant does not have any of the following mutations:
FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Nat'l Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Facility:
Name:
Univ. of California - Irvine
Address:
City:
Irvine
Zip:
92697
Country:
United States
Status:
Recruiting
Facility:
Name:
UCLA Medical Center
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Facility:
Name:
Memorial Cancer Institute
Address:
City:
Pembroke Pines
Zip:
33028
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Chicago
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Facility:
Name:
Robert H. Lurie Comprehensive Cancer Center
Address:
City:
Chicago
Zip:
61612
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Maryland
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Status:
Recruiting
Facility:
Name:
Johns Hopkins University
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Facility:
Name:
Motefiore-Einstein Center for Cancer Care
Address:
City:
Bronx
Zip:
10461
Country:
United States
Status:
Recruiting
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Status:
Recruiting
Facility:
Name:
Weill Cornell Medical College
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Facility:
Name:
Novant Health
Address:
City:
Winston-Salem
Zip:
27103
Country:
United States
Status:
Recruiting
Facility:
Name:
Ohio State University
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Facility:
Name:
Oregon Health and Science University
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Pennsylvania-Abramson CCC-Dept. of Hem Onc
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Facility:
Name:
Thomas Jefferson University Hospital
Address:
City:
Philadelphia
Zip:
19107
Country:
United States
Status:
Recruiting
Facility:
Name:
The University of Texas MD
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Facility:
Name:
The Medical College of Wisconsin- Froedtert Hospital
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Recruiting
Start date:
January 27, 2023
Completion date:
July 31, 2028
Lead sponsor:
Agency:
Astellas Pharma Global Development, Inc.
Agency class:
Industry
Source:
Astellas Pharma Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05520567